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Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread. Cancer Res; 70(17); 6945–56. ©2010 AACR.

Supplementary Figures 1-5 from Reciprocal Activation of Prostate Cancer Cells and Cancer-Associated Fibroblasts Stimulates Epithelial-Mesenchymal Transition and Cancer Stemness

BackgroundETV4 is one of the ETS proteins overexpressed in prostate cancer (PC) as a result of recurrent chromosomal translocations. In human prostate cell lines, ETV4 promotes migration, invasion, and proliferation; however, its role in PC has been unclear. In this study, we have explored the effects of ETV4 expression in the prostate in a novel transgenic mouse model.MethodsWe have created a mouse model with prostate-specific expression of ETV4 (ETV4 mice). By histochemical and molecular analysis, we have investigated in these engineered mice the expression of p21, p27, and p53. The implications of our in vivo findings have been further investigated in human cells lines by chromatin-immunoprecipitation (ChIP) and luciferase assays.ResultsETV4 mice, from two independent transgenic lines, have increased cell proliferation in their prostate and two-thirds of them, by the age of 10 months, developed mouse prostatic intraepithelial neoplasia (mPIN). In these mice,cdkn1aand its p21 protein product were reduced compared to controls; p27 protein was also reduced. By ChIP assay in human prostate cell lines, we show that ETV4 binds to a specific site (-704/-696 bp upstream of the transcription start) in theCDKN1Apromoter that was proven, by luciferase assay, to be functionally competent. ETV4 further controlsCDKN1Aexpression by downregulating p53 protein: this reduction of p53 was confirmed in vivo in ETV4 mice.ConclusionsETV4 overexpression results in the development of mPIN but not in progression to cancer. ETV4 increases prostate cell proliferation through multiple mechanisms, including downregulation ofCDKN1Aand its p21 protein product: this in turn is mediated through direct binding of ETV4 to theCDKN1Apromoter and through the ETV4-mediated decrease of p53. This multi-faceted role of ETV4 in prostate cancer makes it a potential target for novel therapeutic approaches that could be explored in this ETV4 transgenic model.

Simple Summary Metastatic melanoma is one of the most aggressive and lethal malignancies with a poor prognosis. Several data underline the crucial role of amoeboid motility in the dissemination of metastatic melanoma cells. Thus, targeting this phenomenon could represent a promising strategy to prevent metastasis formation and improve metastatic melanoma patient’s survival. With this aim, we investigated the effect of Claisened Hexafluoro, a chemical analogue of Honokiol, on human metastatic melanoma cells. We demonstrated that Claisened Hexafluoro, by deregulating the mitochondrial activity, inhibits amoeboid motility and impairs many steps of the dissemination process, finally decreasing the in vivo metastatic spreading. Collectively, these data suggest possible future applications of Claisened Hexafluoro for the treatment of metastatic melanoma. Abstract Metastatic melanoma is characterized by poor prognosis and a low free-survival rate. Thanks to their high plasticity, melanoma cells are able to migrate exploiting different cell motility strategies, such as the rounded/amoeboid-type motility and the elongated/mesenchymal-type motility. In particular, the amoeboid motility strongly contributes to the dissemination of highly invasive melanoma cells and no treatment targeting this process is currently available for clinical application. Here, we tested Claisened Hexafluoro as a novel inhibitor of the amoeboid motility. Reported data demonstrate that Claisened Hexafluoro specifically inhibits melanoma cells moving through amoeboid motility by deregulating mitochondrial activity and activating the AMPK signaling. Moreover, Claisened Hexafluoro is able to interfere with the adhesion abilities and the stemness features of melanoma cells, thus decreasing the in vivo metastatic process. This evidence may contribute to pave the way for future possible therapeutic applications of Claisened Hexafluoro to counteract metastatic melanoma dissemination.

Our Psychiatry Institute has a long-standing tradition of providing training in the importance of relational and emotional skills and helping relationships. Here we describe techniques that are routinely used on our psychiatric ward (Maggiore della Carita Hospital, Novara, Italy) to promote early rehabilitation of acute psychiatric inpatients. We focus on the Cinema group, which is typical of our approach to informal, therapeutic group activity. Targeting social and relational issues as adjunct to treatment as usual is useful in acute settings and can begin at an early stage of hospitalization. Our intervention is designed to improve patients’ coping strategies, relational and communication skills, and overall quality of life.

In this manuscript, we show the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. uPAR down-regulation by siRNA or its uncoupling from integrins, and hence from integrin-linked tyrosine kinase receptors (IL-TKRs), by an antagonist peptide induced a striking inhibition of the PI3K/AKT/mTOR/HIF1α pathway, resulting into impairment of glucose uptake, decrease of several glycolytic enzymes and of PKM2, a checkpoint that controls metabolism of cancer cells. Further, binding of uPA to uPAR regulates expression of molecules that govern cell invasion, including extracellular matrix metallo-proteinases inducer (EMPPRIN) and enolase, a glycolytyc enzyme that also serves as a plasminogen receptor, thus providing a common denominator between tumor metabolism and phenotypic invasive features. Such effects depend on the α5β1-integrin-mediated uPAR connection with EGFR in melanoma cells with engagement of the PI3K-mTOR-HIFα pathway. HIF-1α trans-activates genes whose products mediate tumor invasion and glycolysis, thus providing the common denominator between melanoma metabolism and its invasive features. These findings unveil a unrecognized interaction between the invasion-related uPAR and IL-TKRs in the control of glycolysis and disclose a new pharmacological target (i.e., uPAR/IL-TKRs axis) for the therapy of melanoma.

Mood disorders represent a major cause of hospitalization in psychiatric ward. We focused on sex differences, therapies and rehospitalization rates/length of stay in inpatients with mood disorders. Rehospitalization is often observed in patients with mental disorders, with rates up to 80%. Socio-demographic features, clinical features and treatment type influence the length of stay. The objective of this study was to assess how the literature findings match everyday clinical practice in an acute psychiatric ward. We performed a retrospective observational study extracting data from our medical records from 1st July 2012 to 1st July 2014. 85 patients were eligible for the study; the overall number of admittances to the ward was 103. We have not found any difference in the rates of Bipolar Disorder between males and females, we failed to find an higher frequency of Depressive disorders in females. In our sample the rates of early readmission is 17.5%. Patients with an involuntary admission included exclusively those with a manic or hypomanic episode; patients with depressive episodes were more likely to have committed a suicide attempt.

OBJECTIVES We assessed sex differences in a sample of first-admission psychiatric inpatients with and without comorbid substance use disorder (SUD) to identify possible risk factors and targets for sex-tailored treatment interventions. METHODS A retrospective study of first admissions to the University Psychiatry Ward, "Maggiore della Carita" Hospital, Novara, Italy, between 2003 and 2012 was accomplished. The clinical charts of patients with (N = 362) and without comorbid SUD (N = 1111) were reviewed. RESULTS Differences in employment, educational, and marital statuses were found between male and female psychiatric patients with and without comorbid SUD. Having a degree was a protective factor for males, whereas it was a risk factor for females. Being divorced and having family problems were both risk factors for comorbidity in females. Regarding the diagnosis, results overlapped in males and females, and both affective and other disorders were risk factors for a comorbid SUD. CONCLUSIONS A significant difference between male and female psychiatric patients with a comorbid SUD was the males' overall poorer psychosocial functioning. Marital status and family problems were risk factors for comorbid SUD in females. Both males and females showed various pathways of access to and choices of substances and, eventually, experienced different impacts on their lives. Hospitalization might help to set up a targeted intervention for patients with comorbidity, while accounting for sex differences. With respect to males, a treatment approach focused on the substance alone might help improve their functioning; females might have a greater benefit from a treatment approach focused on distress, family problems, and relational issues.

Introduction The use of movies in medical (particularly psychiatric) education has been often limited to portraits of mental illness and psychiatrists. The Psychiatric Institute of the Università del Piemonte Orientale has a longstanding tradition of working with/on movies according to a method developed by Eugenio Torre, using dynamic images as educational incitements. Our aim is to describe the preliminary results on the impact of this intervention in medical students. Methods The cinemeducation project lasted 6 months, and included 12 meetings. Forty randomly selected participants were assessed with: Attitudes Towards Psychiatry Scale (ATP-30), Social Distance Scale (SDS), Interpersonal Reactivity Index (IRI), and Toronto Alexithymia Scale (TAS), both at baseline and after 6 months, when the workshop was concluded. Results A significant increase was found in the ATP-30 score, and a reduction of the SDS and IRI-Personal Distress scale scores. Conclusions Informal feedback from participants was strongly positive. Preliminary results from the assessment of participants are encouraging. Students’ attitudes towards psychiatry and ability to tolerate anxiety when experiencing others’ distress improved, while stigma decreased. The evocative power of movie dynamic images, developed in the group and integrated with the help of the group leader, can enrich students’ knowledge, both from a cognitive and emotional standpoint.

Extracellular acidification, a mandatory feature of several malignancies, has been mainly correlated with metabolic reprogramming of tumor cells toward Warburg metabolism, as well as to the expression of carbonic anydrases or proton pumps by malignant tumor cells. We report herein that for aggressive prostate carcinoma, acknowledged to be reprogrammed toward an anabolic phenotype and to upload lactate to drive proliferation, extracellular acidification is mainly mediated by stromal cells engaged in a molecular cross-talk circuitry with cancer cells. Indeed, cancer-associated fibroblasts, upon their activation by cancer delivered soluble factors, rapidly express carbonic anhydrase IX (CA IX). While expression of CAIX in cancer cells has already been correlated with poor prognosis in various human tumors, the novelty of our findings is the upregulation of CAIX in stromal cells upon activation. The de novo expression of CA IX, which is not addicted to hypoxic conditions, is driven by redox-based stabilization of hypoxia-inducible factor-1. Extracellular acidification due to carbonic anhydrase IX is mandatory to elicit activation of stromal fibroblasts delivered metalloprotease-2 and -9, driving in cancer cells the epithelial-mesenchymal transition epigenetic program, a key event associated with increased motility, survival and stemness. Both genetic silencing and pharmacological inhibition of CA IX (with sulfonamide/sulfamides potent inhibitors) or metalloprotease-9 are sufficient to impede epithelial-mesenchymal transition and invasiveness of prostate cancer cells induced by contact with cancer-associated fibroblasts. We also confirmed in vivo the upstream hierarchical role of stromal CA IX to drive successful metastatic spread of prostate carcinoma cells. These data include stromal cells, as cancer-associated fibroblasts as ideal targets for carbonic anhydrase IX-directed anticancer therapies.

Introduction Psychiatric management of inpatients with suicidal behavior involves psychiatrists and psychiatric nurses. Specific precautions should be adopted: observation on a one to one basis with the cooperation of qualified nurses and accommodating the patient in a room close to the infirmary is usually recommended. An ongoing assessment of suicidal risk is warranted to check the response to treatment over time. Aim To compare the severity of depressive symptoms in depressed inpatients admitted after an attempted suicide and in depressed inpatients admitted for any other reason; to assess the severity of attempted suicide and the management of suicidal risk in the clinical setting. Material and method We divided the sample in two subgroups: patients with a diagnosis of depression admitted for a current suicide attempt and depressed patients without a current suicide attempt. Socio-demographic and clinical features were gathered; assessment included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Nurses’ Global Assessment of Suicide Risk (NGASR). Results 46 patients were recruited in a 1-year period and were eligible for our study: 20 had been admitted to the hospital after attempting suicide, while the other 26 had not attempted suicide and were admitted for other reasons related to their depression. The multivariate analysis yielded a statistically significant correlation between the use of antidepressants and current suicide attempt. The occurrence of suicidal attempt was not significantly related to the severity of depressive symptoms. In the current suicide attempters subgroup, NGASR suicide risk levels at discharge were significantly lower than those measured at admission. Current suicide attempters had a higher number of suicide attempts in their clinical history, compared to the other group. Conclusion We found no significant correlation among psychiatric diagnosis, severity of depressive symptoms and current suicide attempt. Antidepressant therapy was found to play the role of protective factor for suicide attempts. History of suicide attempts was one of the major predictor for reattempted suicide. A more thorough understanding of the complex phenomenon of suicide and of the reasons underlying suicidal behaviors is warranted.

This work describes the effectiveness of HDAC-inhibitor (S)-2 towards colorectal cancer (CRC) HCT116 cells in vitro by inducing cell cycle arrest and apoptosis, and in vivo by contrasting tumour growth in mice xenografts. Among the multifaceted drug-induced events described herein, an interesting link has emerged between the oncoprotein histone deacetylase HDAC1 and the oncogenic Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) which is overexpressed in several cancers including CRCs. HDAC1 inhibition by (S)-2 or specific siRNAs downregulates CIP2A transcription in three different CRC cell lines, thus restoring the oncosuppressor phosphatase PP2A activity that is reduced in most cancers. Once re-activated, PP2A dephosphorylates pGSK-3β(ser9) which phosphorylates β-catenin that remains within the cytosol where it undergoes degradation. The decreased amount/activity of β-catenin transcription factor prompts cell growth arrest by diminishing c-Myc and cyclin D1 expression and abrogating the prosurvival Wnt/β-catenin signaling pathway. These results are the first evidence that the inhibition of HDAC1 by (S)-2 downregulates CIP2A transcription and unleashes PP2A activity, thus inducing growth arrest and apoptosis in CRC cells.

It is widely acknowledged that 16% to 34% of suicide attempters repeat a suicide behavior within 1-2 years after the first, “index”, attempt, and that a previous nonfatal suicide attempt is found in up to 40% of suicide deaths (Scoliers, Portzky, van Heeringen & Audenaert, 2009). Suicide attempt is defined as “a self inflicted, potentially injurious behavior with a nonfatal outcome for which there is evidence (either explicit or implicit) of intent to die; a suicide attempt may result in no injuries, or death” (Silverman, Berman Sanddal & O’carroll, 2007).

Introduction Half of cases of Prostate cancer (PC) carry a chromosomal translocation involving one of the genes of the ETS family (ERG, ETV1, ETV4, ETV5, FLI1). Each translocation results in the deregulated expression of an ETS protein in the prostate that, likely, plays a direct role in PC pathogenesis. We have showed that in prostate cell lines ETV4 overexpression increases migration and invasion, and also proliferation, cell cycle progression, anchorage-independent growth, tumor growth in xenograft model. Here we have investigated the effects of ETV4 expression in mouse prostate. Material and Methods The truncated form of ETV4, present in patients, has been cloned under the control a modified rat probasin gene promoter that drives prostate specific expression. By using this construct we have obtained two different transgenic mouse lines with ETV4 specific prostate expression (ETV4-FVB mice). The tissues of these mice have been analyzed by H&E staining and immunohistochemistry. Result and discussion 6 months-old (mo) ETV4-FVB mice did not present prostate lesions, whereas low grade prostatic intraepithelial neoplasia (LGPIN) lesions have been found in about half of 10 mo mice (10 of 18 line C, 4 of 11 line E) and in none of control mice. Since Pten loss is common in PC and it is often associated with ETS translocations, we have investigated the interaction of ETV4 expression with Pten loss by crossing our FVB-ETV4 mice with PTEN+/- mice. Analyzing the progeny of this cross at 7 months of age we found LGPIN in 33% of FVB-ETV4 mice and in 50% of Pten+/- mice, whereas we found multifocal high grade PIN (HGPIN) lesions in all Pten+/-,ETV4 mice (n=9). In addition, at least one LGPIN was found in all 2 months-old Pten+/-,ETV4. Thus, Pten+/-,ETV4 developed early neoplastic lesions whose number and severity increased with age: in fact, HGPIN progressed to locally invasive adenocarcinoma in 12.5% of 7 mo mice and in 50% 10 mo mice. Conclusion These results suggest that ETV4 over-expression is sufficient to initiate neoplastic transformation and cooperates with Pten loss in promoting prostate cancer progression. Thus, also in vivo, ETV4 induces most and perhaps all of the features that make a tumor. Now we are investigating the molecular mechanisms through which ETV4 cooperates with Pten loss to promote cancer progression. These mouse models, in addition to provide insight into PC biology, will be useful to test the effectiveness of experimental therapeutic approaches.

Idiopathic myelofibrosis (IM) is a disease characterized by marrow fibrosis, abnormal stem/progenitor cell trafficking, and extramedullary hematopoiesis frequently associated with alterations in megakaryocytes (Mks). Mice harboring genetic alterations in either the extrinsic (ectopic thrombopoietin expression, TPOhigh mice) or intrinsic (hypomorphic GATA-1 mutation, GATA-1low mice) control of Mk differentiation develop myelofibrosis, a syndrome similar to IM. The relationship, if any, between the pathobiologic mechanism leading to the development of myelofibrosis in the 2 animal models is not understood. Here we show that plasma from GATA-1low mice contained normal levels of TPO. On the other hand, Mks from TPO-treated wild-type animals (TPOhigh mice), as those from GATA-1low animals, had similar morphologic abnormalities and contained low GATA-1. In both animal models, development of myelofibrosis was associated with high transforming growth factor β1 (TGF-β1) content in extracellular fluids of marrow and spleen. Surprisingly, TPO treatment of GATA-1low mice restored the GATA-1 content in Mks and halted both defective thrombocytopoiesis and fibrosis. These data indicate that the TPOhigh and GATA-1low alterations are linked in an upstream-downstream relationship along a pathobiologic pathway leading to development of myelofibrosis in mice and, possibly, of IM in humans.

Despite the lack of extrapyramidal side effects, some atypical antipsychotics can induce an increase in prolactinemia, as the conventional neuroleptics do. We decided to evaluate the effects of risperidone on serum prolactin levels and prolactin-related adverse effects in 20 outpatients of an Italian community psychiatric service. Patients enrolled in this study were on risperidone (2–8 mg per day; mean dose=4.15±0.4 mg per day) treatment in the period May–November 2002. The 20 patients, 13 women and 7 men (mean age=36.38±3.2 years for women and 29.7±2.2 for men) who accomplished inclusion criteria, participated in the study after giving informed written consent. Raised prolactin levels were observed in 13 (9 women and 4 men) out of 20 patients, but only 8 patients presented prolactin-related adverse effects, libido reduction being the most frequent. In this observational study, risperidone enhanced serum prolactin in 65% of patients. A good correlation was found between age and prolactin levels in pre-menopausal women, although no clear correlation among duration of treatment, dose used, prolactin levels and prolactin-related adverse effects could be established.

The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating pericyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that derives from sphingomyelin catabolism and regulates biological functions in cell survival, proliferation, and differentiation. In this study, we aimed to identify the role of S1P axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (H-MVEC)) in the formation of capillary-like structures. We demonstrated that the S1P biosynthetic pathway brought about by sphingosine kinases (SK) SK1 and SK2 as well as spinster homolog 2 (SPNS2) transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers and for the formation and stabilization of capillary-like structures in a 3D Matrigel culture. Moreover, the conditioned medium (CM) harvested from H-MVEC, where SK1, SK2, and SPNS2 were down-regulated, exerted a significantly diminished effect on MAB capillary morphogenesis and migration. Notably, we demonstrated that S1P1 and S1P3 receptors were positively involved in CM-induced capillary-like formation and migration, while S1P2 exerted a negative role on CM-induced migratory action of MAB. Finally, SK inhibition as well as MAB S1P1 and S1P3 down-regulation impaired H-MVEC-MAB cross-talk significantly reducing in vivo angiogenesis evaluated by Matrigel plug assay. These findings individuate novel targets for the employment of MAB in vascular-related pathologic conditions. • Down-regulation of SK1/2 in H-MVEC impaired vessel formation when cultured with MAB. • H-MVEC SPNS2 is critical for morphogenesis and migration induced by H-MVEC CM of MAB. • CM from SK1- and SK2-siRNA H-MVEC impaired morphogenesis and migration of MAB. • S1P1/3 were involved on CM-induced morphogenesis and migration of MAB. • Matrigel plug assay showed the role of S1P axis in MAB-endothelial cell interaction.

To assess psychopathology, personality and theory of mind in a sample of university students, and to analyse their correlation with socio-demographic and academic factors.Socio-demographic and academic data were collected from 228 students. They completed the Eysenck Personality Questionnaire-R, Symptom Checklist-90-R (SCL-90-L) and Theory of Mind (ToM) test.Elevated psychological distress was found in 38.6% of students; 30.3% had an abnormal ToM score. Students with an abnormal ToM score had a significantly lower probability than those with normal ToM test to repeat an exam three times or more. Not being married and receiving psychiatric care significantly influenced the probability of repeating an exam. Abnormal ToM students had specific features as far as major and SCL-90-R scores are concerned.A correlation was found among ToM performance and some indicators of academic performance. Students with ToM scores under the cut-off reported more psychopathological symptoms and distress. Implications are discussed

The liaison psychiatry defines itself as way to comprehend the psychological aspects in any situation of care, and in particular in the context of somatic care. The identification of the psychic processes, which can influence the diagnosis and the outcome of a somatic disease, is essential to adequately and globally take care of the individual. At the same time, training in the Help relationship allows to identify the difficulties of nursing, which is very often source of exhaustion and burn-out.

BACKGROUND: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. METHODS: 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. RESULTS: CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. CONCLUSIONS: PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.

We have previously shown that peculiar metabolic features of cell adaptation and survival in hypoxia imply growth restriction points that are typical of embryonic stem cells and disappear with differentiation. Here we provide evidence that such restrictions can be exploited as specific antiblastic targets by physiological factors such as pyruvate, tetrahydrofolate, and glutamine. These metabolites act as powerful cytotoxic agents on cancer stem cells (CSCs) when supplied at doses that perturb the biochemical network, sustaining the resumption of aerobic growth after the hypoxic dormant state. Experiments were performed in vivo and in vitro using CSCs obtained from various anaplastic tumors: human melanoma, leukemia, and rat hepatoma cells. Pretreatment of melanoma CSCs with pyruvate significantly reduces their self-renewal in vitro and tumorigenicity in vivo. The metabolic network underlying the cytotoxic effect of the physiological factors was thoroughly defined, principally using AH130 hepatoma, a tumor spontaneously reprogrammed to the embryonic stem stage. This network, based on a tight integration of aerobic glycolysis, cellular redox state, and folate metabolism, is centered on the cellular NADP/NADPH ratio that controls the redox pathway of folate utilization in purine synthesis. On the whole, this study indicates that pyruvate, FH 4, and glutamine display anticancer activity, because CSCs are committed to survive and maintain their stemness in hypoxia. When CSC need to differentiate and proliferate, they shift from anaerobic to aerobic status, and the few mitochondria available makes them susceptible to the injury of the above physiological factors. This vulnerability might be exploited for novel therapeutic treatments.

Topiramate is a new anti convulsant agent that acts on the voltage-activated sodium channels and on the glutamate and GABA receptors; it is furthermore able to reduce hunger and therefore contributes to loss of weight. The authors report the case of a patient suffering from binge eating disorder, who was unresponsive to several therapeutic plans but was successfully treated with topiramate.

Tumor cell plasticity largely depends on epithelial-to-mesenchymal transition (EMT) and its reversion. It was ascertained that EMT characterizes disease progression, including melanoma malignancy. As most solid tumors, melanoma shows extracellular acidosis, we analyse the impact of acidic environment on the EMT development in human melanoma cells. Melanoma cells were exposed to an acidic extracellular environment (pH 6.7) and tested for EMT markers. We found that acidic cells express a significant up-regulation of mesenchymal markers (N-cadherin, Vimentin), transcription factors (Twist, NF-κB) and a significant, although modest, reduction of E-cadherin expression. Acidic cell also express an increased invasiveness through Matrigel associated with an up-regulation of MMP-9 activity. When we injected acidic cells intravenously into immunodeficient animals, we found a number of lung micrometastases not different from non-acidic cells. Indeed, they show a partial G1 cell cycle arrest, which might interfere with the growth of lung colonies. When we investigated the in vitro invasiveness and lung colonization of a mixed population of acidic and non acidic melanoma cells, we found that acidic cells promote in vitro invasiveness of non-acidic cells and this cooperation leads to an higher migration rate than acidic cells. Moreover, acidic cells cooperate for a better lung colonization of non-acidic cells, that represent the greater part of cells participating to lung micrometastases. We found evidence that acidity triggers in melanoma cells an EMT program, which although "incomplete", potentiates migration rate and development of lung colonies into immunodeficient host of cells grown in standard pH.

Background Medical schools are currently charged with a lack of education as far as empathic/relational skills and the meaning of being a health-care provider are concerned, thus leading to increased interest in medical humanities. Discussion Medical humanities can offer an insight into human illness and in a broader outlook into human condition, understanding of one self, responsibility. An empathic relation to patients might be fostered by a matching approach to humanities and sciences, which should be considered as subjects of equal relevance, complementary to one another. Recently, movies have been used in medical – especially psychiatric - trainees education, but mainly within the limits of teaching a variety of disorders. A different approach dealing with the use of cinema in the training of psychiatry residents is proposed, based on Jung and Hillman’s considerations about the relation between images and archetypes, archetypal experience and learning. Summary Selected full-length movies or clips can offer a priceless opportunity to face with the meaning of being involved in a care-providing, helping profession.

IntroductionThe effects of psychotropic drugs and alcohol acute intoxication are important risk factors for attempted suicide among individuals with and without substance use disorder (SUD).AimsThe first aim of this study is describing the socio-demographic features and clinical history of subjects who were acutely intoxicated when attempting suicide. The second aim is to compare their features with those of subjects without acute alcohol and substances intoxication at suicide attempt time.MethodsDeterminants of ER psychiatric consultations were studied prospectively during the period 2008–2014 at the “Maggiore della Carità” Hospital in Novara, Italy. For each patient, a data sheet was filled in by experienced psychiatrists, in order to gather demographic features, psychiatric history and present clinical issues like blood and urine dosage of amphetamine and methamphetamine, cannabinoid, cocaine and alcohol. Comparison of qualitative data was performed by means of the Chi2 test. Statistical significance was set at P ≤ 0.05.ResultsWe collected a sample of 495 suicide attempters who referred to our ER. Statistical analysis of demographic and clinical data is still ongoing.ConclusionsPreliminary results point out that acute alcohol and drugs intoxication at suicide attempt time is much more frequent in subjects without a SUD. Implications will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionStudies conducted on Italian samples suggested that 70% of self-harms referred to the emergency room (ER) were suicide attempts. Suicide attempts are associated with societal, relationship and individual risk factors, which vary with age and gender, occur in combination, and may change over time. We conducted a previous study on a sample of psychiatric consultations in ER from 2008 to 2011. We observed that female gender, a permanent job and being in the warmer months of the year were risk factors for suicide attempts.AimTo update knowledge about risk factors for attempted suicide analyzing a larger sample of ER psychiatric consultations.MethodsDeterminants of emergency room visits for psychiatric reasons were studied prospectively in a period of 8 years, from 2008 to 2015 at the “Maggiore della Carità” Hospital in Novara. The psychiatric assessment of patients was performed by experienced psychiatrists with a clinical interview. For each patient, a data sheet was filled in order to gather demographic and clinical features. Comparison of qualitative data was performed by means of the Chi2 test while differences between groups for continuous variables were assessed through a t-test. Statistical significance was set at P ≤ 0.05. A multivariate analysis was performed using logistic regression in order to assess the potential predictors of attempted suicide. Results are expressed as odds ratio (OR) with 95% confidence intervals (95% CI).ConclusionsWe have collected data from more than 500 psychiatric consultations for attempted suicide. Data collection and statistical analyses are still ongoing. Implications will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

BackgroundMental disorders are considered a risk factor for suicide: for example, the lifetime risk of suicide is estimated to be 4%–8% in people with mood disorders. The literature suggests that a history of suicide attempts is significantly related to electrodermal hyporeactivity and that patients with violent suicide attempters exhibit faster habituation of the electrodermal response to repeated neutral tones than patients with non-violent attempts. The impact of depressive symptoms on suicidal ideation may be moderated by resilience. Resilience refers to the ability to maintain o regain mental health despite experiencing adversity. In bipolar and depressive disorders, resilience may influence severity of episodes, frequency of relapse and response to treatment.AimThe objective of our study was to assess the possible correlation among attempted suicide, resilience and dermal reactivity in a sample of depressed patients.MethodsWe recruited patients with depressive disorders and bipolar depression; data about socio-demographic, clinical features, severity of attempted suicide and suicidal risk were gathered. Patients filled in the Resilience Scale for Adult (RSA). Moreover, for each patient we performed the Edor test in order to assess dermal reactivity.ResultsData collection is still ongoing. We expect to find lower levels of resilience in those patients who are hyporeactive and attempted suicide. Moreover, we hypothesize that suicide attempts in the group of hyporeactive patients would be characterized by planning and greater severity. Clinical implications will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionAccording to Durkheim's theory, suicide attempts increase during periods of rapid economic changes and decrease again when stability is achieved, due to the social integration in the community guaranteed by occupational status. Since 2009 in Europe, it was observed an increase in the suicide rates, in line with the increase of unemployment. Although unemployment is considered a risk factor for suicide, it was observed a noticeable increase in suicide rates among Italian employed men during the last years, probably related to the specific economic scenario and to emerging difficulties in keeping an income to adequately maintain one's own family standard of living.AimTo study attempted suicides with a specific focus and attention on the current Italian economic scenario.MethodsDeterminants of emergency room visits for psychiatric reasons in patients aged > 16 years were studied prospectively from 2008 to 2015 at the AOU Maggiore della Carità Hospital, Novara, Italy. Each patient was assessed by an experienced psychiatrist with a clinical interview and socio-demographic and clinical features were gathered. Statistical significance was set at P ≤ 0.05.ResultsPreliminary results suggest an increase in suicide attempts according to the rise of the unemployment rate in Novara. Although in absolute figures most attempters are unemployed, it seems that suicide attempts are more frequent in the group of employed subjects, which includes also people under redundancy fund. This subgroup may be considered halfway between employed and unemployed attempters.ConclusionsData collection and statistical analyses are still ongoing. Implications for clinical practice will be discussed.Disclosure of interestThe authors have not supplied their declaration of competing interest.

BackgroundHistory of previous suicide attempts is one of the most important risk factors for a subsequent completed suicide. Suicide reattempters (SR) has been long associated with demographic and clinical risk factors for suicide, such as unemployment and psychiatric disorders, however a recent review of the literature has not supported a specific age and gender profile of SR, but rather underscored that, as far as diagnosis is concerned, SR were more likely to have a personality disorder. According to literature, 16%–34% of the subjects repeat a suicide attempt within the first 2 years after the previous one.AimThe purpose of our study was evaluating clinical and socio-demographic characteristics and the outcome of psychiatric consultation among subjects referring to an emergency room for recommitting a suicide attempt.MethodsWe considered a sample of SR aged > 16 years. We extracted data from the database including all patients requiring psychiatric evaluation in the emergency room, and eventually compared the features of SR and patients with a single suicide attempt. For each patient, we gathered socio-demographic features, psychiatric history and current clinical issues, suicidal intent and suicidal behaviors.ResultsData collection and statistical analyses are still ongoing. Preliminary results show that, compared to patients with a single suicide attempt, SR were more frequent female, unmarried, employed, with a low level of instruction; they had a psychiatric disease (axis I – anxiety disorder, somatoform disorder; axis II – histrionic personality disorder); they are under the care of mental health services and under psychopharmacological treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

BackgroundTGFß overproduction in cancer cells is one of the main characteristics of late tumor progression being implicated in metastasis, tumor growth, angiogenesis and immune response. We investigated the therapeutic efficacy of anti-TGFß peptides in the control of angiogenesis elicited by conditional over-expression of TGFß.MethodsWe have inserted in human MCF7 mammary-cancer cells a mutated TGFß gene in a tetracycline-repressible vector to obtain conditional expression of mature TGFß upon transient transfection, evaluated the signaling pathways involved in TGFß-dependent endothelial cells activation and the efficacy of anti-TGFß peptides in the control of MCF7-TGFß-dependent angiogenesis.ResultsTGFß over-expression induced in MCF7 several markers of the epithelial-to-mesenchymal transition. Conditioned-medium of TGFß-transfected MCF7 stimulated angiogenesis in vivo and in vitro by subsequent activation of SMAD2/3 and SMAD1/5 signaling in endothelial cells, as well as SMAD4 nuclear translocation, resulting in over-expression of the pro-angiogenic growth and differentiation factor-5 (GDF5). Inhibition or silencing of GDF5 in TGFß-stimulated EC resulted in impairment of GDF5 expression and of TGFß-dependent urokinase-plasminogen activator receptor (uPAR) overproduction, leading to angiogenesis impairment. Two different TGFß antagonist peptides inhibited all the angiogenesis-related properties elicited in EC by exogenous and conditionally-expressed TGFß in vivo and in vitro, including SMAD1/5 phosphorylation, SMAD4 nuclear translocation, GDF5 and uPAR overexpression. Antagonist peptides and anti-GDF5 antibodies efficiently inhibited in vitro and in vivo angiogenesis.ConclusionsTGFß produced by breast cancer cells induces in endothelial cells expression of GDF5, which in turn stimulates angiogenesis both in vitro and in vivo. Angiogenesis activation is rapid and the involved mechanism is totally opposed to the old and controversial dogma about the AKL5/ALK1 balance. The GDF-dependent pro-angiogenic effects of TGFß are controlled by anti-TGFß peptides and anti-GDF5 antibodies, providing a basis to develop targeted clinical studies.

Dry eye syndrome (DES) or keratoconjunctivitis sicca is an eye disease caused by the chronic lack of lubrication and moisture of the eye. The pathogenesis of DES involves the over-expression and over-activity of corneal Matrix Metalloproteinase 9 (MMP-9). We propose herein a new, non-symptomatic approach for the treatment of DES based on the inhibition of MMP-9 by a new highly soluble molecule, designed as PES_103 that has been shown to inhibit MMP-9 both in vitro and in vivo. The efficacy of PES_103 in vivo and the potential benefits of this treatment in restoring tear production were studied in this work using an animal model of reduced lacrimation. PES_103 did not show any significant corneal toxicity.

""\\"Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and\\\\\\\/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++) -chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4- but not (R)-2 - caused G0\\\\\\\/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg\\\\\\\/kg\\\\\\\/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral\\\\\\\/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy.\\"""

The “angiogenic switch” during tumor progression is increasingly recognized as a milestone event in tumorigenesis, although the surprising prometastatic effect of antiangiogenic therapies has recently shaken the scientific community. Tumor hypoxia has been singled out as a possible responsible factor in this prometastatic effect, although the molecular pathways are completely unknown. We report herein that human melanoma cells respond to hypoxia through a deregulation of the mitochondrial release of reactive oxygen species (ROS) by the electron transfer chain complex III. These ROS are mandatory to stabilize hypoxia-inducible factor-1α (HIF-1α), the master transcriptional regulator of the hypoxic response. We found that melanoma cells sense hypoxia-enhancing expression/activation of the Met proto-oncogene, which drives a motogenic escape program. Silencing analyses revealed a definite hierarchy of this process, in which mitochondrial ROS drive HIF-1α stabilization, which in turn activates the Met proto-oncogene. This pathway elicits a clear metastatic program of melanoma cells, enhancing spreading on extracellular matrix, motility, and invasion of 3D matrices, as well as growth of metastatic colonies and the ability to form capillary-like structures by vasculogenic mimicry. Both pharmacological and genetic interference with mitochondrial ROS delivery or Met expression block the hypoxia-driven metastatic program. Hence, we propose that hypoxia-driven ROS act as a primary driving force to elicit an invasive program exploited by aggressive melanoma cells to escape from a hypoxic hostile environment.

Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread. Cancer Res; 70(17); 6945–56. ©2010 AACR.

Proteases are considered critical in peri-cystic tissue degradation required in jaw cyst expansion. We studied the expression of the plasminogen activation system (plasminogen activators; their inhibitor type-1, PAI-1; the receptor for the urokinase-type plasminogen activator, uPAR) in follicular and inflammatory cysts of the jaw, to identify a possible role of this system in jaw cyst enlargement.Jaw cysts were collected by therapeutic enucleation. ELISA and casein zymography were used to measure and characterize plasminogen activators in cyst fluid. By immunohistochemistry we examined the presence of uPAR in cyst walls and inflammatory cells, and by Western blotting the molecular forms of uPAR within the cyst fluid.Inflammatory cysts fluid contained higher amounts of plasminogen activators of the urinary-type (uPA), and lower amounts of PAI-1, when compared to follicular cysts fluid. Epithelial layers of both types of cysts and inflammatory cells expressed uPAR. Native 3-domain uPAR was scarcely detectable within cysts, where its cleavage was accounted for by uPA.These data suggest a plasminogen activation-dependent mechanism of cyst enlargement, where only the outward uPAR expressed on epithelial cells and on inflammatory cells direct the peri-cystic protease cascade, in a way similar to tumor enlargement within tissues.

Background and Objectives: 1) To identify the sociodemographic, anamnestic characteristics and presentation symptoms of patients, at the time of first hospitalization, associated with a discharge diagnosis of schizophrenic versus non-schizophrenic psychoses; 2) to define risk factors, at the time of the first admission, for a rehospitalization, regardless of reasons for readmission; 3) to assess the diagnostic stability between first and second hospitalization. Methods: This study includes 245 patients first admitted to the University Psychiatric Clinic of Novara in a period of seven years, discharged with a diagnosis of psychosis as reported in the Discharge Register (ICD-9-CM codes 290-299). Data were collected by consulting medical records and registers of community-based services of the South Novara Mental Health Department. A logistic regression model was used to determine the characteristics associated with a discharge diagnosis of schizophrenia. The relationship between the risk of rehospitalization and patients characteristics was studied using Cox,s regression analysis. Results: Risk factors for a discharge diagnosis of schizophrenia were age, compulsory admission, positive symptoms, and previous non-psychotic psychiatric episodes. Risk factors for rehospitalization were a diagnosis of schizophrenia, an age of less than 40 years, the absence of a stable affective relationship, and living with the family of origin. The 92% of the patients diagnosed as schizophrenic on the first hospitalization had the same diagnosis on readmission. Conclusions: Schizophrenia differs from other psychoses in terms of the greater prevalence of both some symptomatological characteristics and an history of previous non psychotic episodes. Some sociodemographic and clinical characteristics at the time of the first hospitalization can provide indications useful in preventing rehospitalization.

Purpose Suicide attempts are extremely prevalent and associated with many risk factors that vary with age and gender, occur in combination, and may change over time. The aim of the present study was to describe gender differences among psychiatric ER users at the AOU Maggiore della Carita Hospital in Novara for attempted suicide with regard to intentions and methods of attempting. Methods Determinants of ER psychiatric consultations were studied prospectively during the period 2008-2014 at the 'Maggiore” Hospital in Novara. Comparison of qualitative data was performed by means of the ×2 test. Statistical significance was set at p≤0.05. Results We have already gathered data from more than 2000 ER psychiatric consultations. Preliminary results suggest that suicide attempts are more common in females than in males, although through the years there seems to be a trend towards increase of attempts even in males. Surprisingly, suicide attempts are found to be more common in employed subjects than in unemployed ones. Reasons for self-harming are associated with relational problems rather than psychiatric symptoms. Drugs poisoning seems to be the preferred suicide method. Conclusions The results described above should be considered as preliminary, as data collection and statistical analyses are still ongoing. Anyway, the possible correlation between employment and suicide attempt, and the growing frequency of attempts in males seem to be particularly interesting. Implications will be discussed.

Introduction Our Psychiatry Ward (SC Psichiatria, Maggiore della Carita Hospital, Novara) has a longstanding tradition in the training of clinicians (psychiatrists, but also non-psychiatrists) about the importance of the approach in helping relationships. This tradition reflects itself in the organization of the assistance to the acute psychiatric inpatients admitted to the Ward. In addition to treatment as usual, patients have the opportunity of being involved in several group activities. The activities are proposed to them, with an approach that varies according to the patient's lifetime diagnosis, current conditions, relational difficulties, etc. In other words, different activities may be proposed to different patients, in different ways. Aims To describe the integrated treatment approach we use in our Psychiatry Ward. Methods Group activities are guided by a group leader who is supported by one or two assistants whose role is to facilitate discussion. Activities include: Newspaper Reading (everyday in the morning, 1 hour); Music Listening Group (once a week; 1 hour); Cinema Group (once a week; 2 hours and a half); Fairytale Group (on alternating days in the evening, 1 hour). Results More details will be supplied regarding the theoretical background for the group, the group features/implementation, and its specific objectives. Conclusions All the group activities integrate themselves in an early rehabilitation project tailored to each patients' characteristics and needs. Briefly, their main objectives include: 1) to help patients endorse their cognitive, emotional and relational skills; 2) to offer support to the crisis they are experiencing, which led them to admission to the Ward.

Introduction Our Psychiatry Ward offers several group activities to both inpatients and outpatients. Among these, the Editorial Group involves only outpatients (who had been previously admitted to the Psychiatry Ward as inpatients) in fair psychopathological compensation, carefully selected for this long-term rehabilitation approach. Aims To describe the Editorial Group activity. Methods The Editorial Group meets once a week at the Psychiatry Ward. It involves patients, nurses and a group leader who is a Psychiatrist. The psychiatrists' and nurses' role is to facilitate the group process and the exploration of the topics discussed. Members are encouraged to discuss their opinions about tales, movies and books; to share poems, paintings, photographs. The aim of this process is to eventually develop a Ward magazine which is published quarterly. Results Members' commitment is extended beyond the weekly meeting hour of the group; indeed, we have observed that patients in their free time spontaneously decide to spend time collecting material to share and drawing up the articles, which are assigned according to patients' aptitudes and preferences. A continued commitment to share daily life experiences and to express creativity, helps patients get involved in the Group, and eventually leads to something concrete and valuable to share with others, also beyond the Group. Both the leader and the other equipe members help patients listening to each others' opinions, ideas and personal experiences. Conclusions The Editorial Group helps patients improving emotional and relational skills, and stimulates cognitive resources. Moreover, it enhances creativity, promotes collaboration and stimulates curiosity.

The main epiluminescence microscopy (ELM) patterns observed on volar acquired melanocytic naevi are the parallel-furrow, the lattice-like and the fibrillar patterns. Because of the peculiar arrangement and configuration of epidermal rete ridges in the glabrous skin, the traditional histological picture does not provide an exact correlation with ELM features. In particular, the fibrillar pattern lacks a histopathological correlate. To clarify the microscopic features of the fibrillar pattern, we used transverse histological sectioning to study an acquired compound melanocytic naevus of the sole, characterized by a mixed parallel-furrow/fibrillar pattern on ELM. Low-magnification images of transverse sections allowed us to highlight the typical anatomical arrangement of the volar skin clearly, while high-magnification images demonstrated that the fibrillar pattern corresponded to parallel striae of intensely pigmented corneocytes arranged obliquely to the cutaneous surface.

Introduction: We collected the data relating to involuntary hospital treatment (IHT) in the University Psychiatric Ward at Novara Hospital between 1991 and 2002, and compared them with those relating to Piedmont and the whole of Italy. Methods: The data were collected from the ward medical records. Results: IHT was much more frequent among young male schizophrenics living with their families of origin. Most of the subjects were not working at the time of admission. There was a statistically significant correlation between male gender and the risk of being admitted for a period of less than 12 days. The risk of being admitted for more than 12 days significantly correlated with the province of birth and residence, as well as with a diagnosis of schizophrenic psychosis. Conclusions: Schizophrenia is the diagnosis that is most frequently associated with IHT.

Background to investigate the suicide phenomenon among the elderly (people aged 65 and over) in the Italian provinces of Novara and Verbania, in the time span between January 1990 and December 2000, in order to evaluate if the characteristics of the suicide behaviour correlate to the place of living with particular attention to the psychosocial factors. Methods the information was collected from the Republic Procuration of the two provinces. Frequencies and contingency tables were evaluated to compare the data found in the two provinces. Standardised Mortality Ratios (SMRs) with their confidential intervals (95% confidence intervals) were calculated in comparison with the average suicide rates in North West Italy in the same period and in the same age group. Results One hundred and eighty-four suicides were committed from the elderly, with an average rate of 14.07 per 100 000 inhabitants in Novara and 25.56 in Verbania. The most common methods used to commit suicide were hanging and jumping from height. The factors chiefly related to suicide were mental disease, followed by organic illness. The analysis of SMRs point out that the incidence of suicide in the province of Verbania is higher than in North West Italy while in Novara it is lower. Conclusion the evaluation of the suicide risk in the elderly in a diagnostic and preventive framework must take into consideration the psychosocial factors that vary with the place of living. Copyright © 2005 John Wiley & Sons, Ltd.